In 2001, trilostane, a synthetic steroid analogue, was licensed in the United Kingdom for treating canine pituitary-and adrenal-dependent hyperadrenocorticism. Trilostane is currently undergoing Food and Drug Administration (FDA) review for the same purposes in the United States. In this article, I briefly review the diagnosis and treatment of hyperadrenocorticism and then present the current knowledge on trilostane, discuss therapeutic considerations, and address possible adverse effects.

HYPERADRENOCORTICISM

Hyperadrenocorticism is a clinical syndrome arising from chronic, excessive exposure to glucocorticoids. It is also referred to as Cushing's syndrome in recognition of the work done by Dr. Harvey Cushing, a pioneering neurosurgeon, in the early 1900s. There are three types of hyperadrenocorticism. >

Table 1 Clinical Signs of Hyperadrenocorticism

Pituitary-dependent hyperadrenocorticism (PDH) involves excessive cortisol secretion in response to an inappropriate release of adrenocorticotropic hormone (ACTH) by a pituitary tumor (usually a benign adenoma). This form of hyperadrenocorticism is also called Cushing's disease.

Adrenal-dependent hyperadrenocorticism involves excessive cortisol secretion by an adrenocortical tumor and can be benign or malignant.

Iatrogenic hyperadrenocorticism is due to exogenous glucocorticoid administration—oral, parenteral, or topical. It resolves when glucocorticoids are discontinued.

Diagnosis

Table 2 Laboratory Abnormalities Associated with Hyperadrenocorticism

In patients with the clinical signs of hyperadrenocorticism (Table 1) and supportive findings on routine laboratory tests (Table 2), the diagnosis must be confirmed before therapy is considered.

Table 3 ACTH Stimulation Testing Methodology and Interpretation

The two screening tests commonly used to diagnose hyperadrenocorticism are the ACTH stimulation test and the low-dose dexamethasone suppression test. The ACTH stimulation test (Table 3)1 is quicker and requires less venipuncture, but it may be less sensitive than the low-dose dexamethasone suppression test is.2 However, it is the only way to identify a patient with iatrogenic hyperadrenocorticism, and it provides information for post-treatment comparisons. The advantage of the low-dose dexamethasone suppression test (Table 4) is its potential for differentiating PDH from adrenocortical tumors.3

It is important to determine whether a patient has PDH or an adrenocortical tumor. The easiest way to answer this question is by performing an abdominal ultrasonographic examination. A competent scanner can easily identify both adrenal glands and assess their size and shape. Bilaterally normal or enlarged glands support PDH; asymmetry with a mass on one gland and atrophy of the other gland indicates an adrenocortical tumor. Other ways to differentiate between PDH and an adrenocortical tumor include measuring endogenous ACTH concentrations (normal or elevated in patients with PDH, low in patients with hyperadrenocorticism due to an adrenocortical tumor) and performing a high-dose dexamethasone suppression test (suppression supports a diagnosis of PDH). Abdominal radiography may reveal calcification associated with an adrenal mass but is not a sensitive test for this purpose.